Hirst D G, Vojnovic B, Stratford I J, Travis E L
Br J Cancer Suppl. 1978 Jun;3:237-41.
The clinical use of misonidazole as a hypoxic cell radiosensitizer is at present limited by its neurotoxicity at high doses (Urtasun et al., 1977; Dische et al., 1977). An in vivo neurological end point, viz. measurement of nerve conduction velocity, has been developed to examine sensitizer action. Conduction velocity in mice was measured as a function of time after a single dose of misonidazole and as a function of drug dose. Doses greater than 0.33 mg/g produced significant transient reductions in velocity. The time course of the reduction in velocity closely followed the uptake/excretion profile of misonidazole from blood serum.
目前,米索硝唑作为一种乏氧细胞放射增敏剂的临床应用受到其高剂量时神经毒性的限制(乌尔塔孙等人,1977年;迪谢等人,1977年)。已开发出一种体内神经学终点指标,即测量神经传导速度,以检查增敏剂的作用。在单次给予米索硝唑后,测量小鼠的神经传导速度随时间的变化以及随药物剂量的变化。剂量大于0.33毫克/克时,会导致速度出现显著的短暂降低。速度降低的时间进程与米索硝唑从血清中的摄取/排泄情况密切相关。